Effects of Homocysteine Lowering With B Vitamins on Cognitive Aging: Meta-Analysis of 11 Trials With Cognitive Data on 22,000 Individuals

Am J Clin Nutr. 2014 Aug;100(2):657-66. doi: 10.3945/ajcn.113.076349. Epub 2014 Jun 25.

Abstract

Background: Elevated plasma homocysteine is a risk factor for Alzheimer disease, but the relevance of homocysteine lowering to slow the rate of cognitive aging is uncertain.

Objective: The aim was to assess the effects of treatment with B vitamins compared with placebo, when administered for several years, on composite domains of cognitive function, global cognitive function, and cognitive aging.

Design: A meta-analysis was conducted by using data combined from 11 large trials in 22,000 participants. Domain-based z scores (for memory, speed, and executive function and a domain-composite score for global cognitive function) were available before and after treatment (mean duration: 2.3 y) in the 4 cognitive-domain trials (1340 individuals); Mini-Mental State Examination (MMSE)-type tests were available at the end of treatment (mean duration: 5 y) in the 7 global cognition trials (20,431 individuals).

Results: The domain-composite and MMSE-type global cognitive function z scores both decreased with age (mean ± SE: -0.054 ± 0.004 and -0.036 ± 0.001/y, respectively). Allocation to B vitamins lowered homocysteine concentrations by 28% in the cognitive-domain trials but had no significant effects on the z score differences from baseline for individual domains or for global cognitive function (z score difference: 0.00; 95% CI: -0.05, 0.06). Likewise, allocation to B vitamins lowered homocysteine by 26% in the global cognition trials but also had no significant effect on end-treatment MMSE-type global cognitive function (z score difference: -0.01; 95% CI: -0.03, 0.02). Overall, the effect of a 25% reduction in homocysteine equated to 0.02 y (95% CI: -0.10, 0.13 y) of cognitive aging per year and excluded reductions of >1 mo per year of treatment.

Conclusion: Homocysteine lowering by using B vitamins had no significant effect on individual cognitive domains or global cognitive function or on cognitive aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging*
  • Cognition
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / prevention & control*
  • Dietary Supplements*
  • Evidence-Based Medicine*
  • Homocysteine / antagonists & inhibitors*
  • Homocysteine / blood
  • Humans
  • Hyperhomocysteinemia / blood
  • Hyperhomocysteinemia / diet therapy*
  • Hyperhomocysteinemia / physiopathology
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Vitamin B Complex / therapeutic use*

Substances

  • Homocysteine
  • Vitamin B Complex